Cellular FXIII in Human Macrophage-Derived Foam Cells

Laura Somodi, Emőke Horváth, Helga Bárdos, Barbara Baráth, Dávid Pethő, Éva Katona, József Balla, Nicola J Mutch, László Muszbek

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Macrophages express the A subunit of coagulation factor XIII (FXIII-A), a transglutaminase which cross-links proteins through Nε-(γ-L-glutamyl)-L-lysyl iso-peptide bonds. Macrophages are major cellular constituents of the atherosclerotic plaque; they may stabilize the plaque by cross-linking structural proteins and they may become transformed into foam cells by accumulating oxidized LDL (oxLDL). The combination of oxLDL staining by Oil Red O and immunofluorescent staining for FXIII-A demonstrated that FXIII-A is retained during the transformation of cultured human macrophages into foam cells. ELISA and Western blotting techniques revealed that the transformation of macrophages into foam cells elevated the intracellular FXIII-A content. This phenomenon seems specific for macrophage-derived foam cells; the transformation of vascular smooth muscle cells into foam cells fails to induce a similar effect. FXIII-A containing macrophages are abundant in the atherosclerotic plaque and FXIII-A is also present in the extracellular compartment. The protein cross-linking activity of FXIII-A in the plaque was demonstrated using an antibody labeling the iso-peptide bonds. Cells showing combined staining for FXIII-A and oxLDL in tissue sections demonstrated that FXIII-A-containing macrophages within the atherosclerotic plaque are also transformed into foam cells. Such cells may contribute to the formation of lipid core and the plaque structurization.

Original languageEnglish
Article number4802
JournalInternational Journal of Molecular Sciences
Issue number5
Publication statusPublished - 2 Mar 2023

Bibliographical note

Funding Information:
The research was funded by grants from the National Research, Development, and Innovation Office (NKFIH) (K129287), by the GINOP 2.3.2-15-2016-00050 project co-financed by the European Union and the European Regional Development Fund, and by the Hungarian Academy of Science (11014 project). J.B. and D.P. were supported by Eötvös Loránd Research Network (11003). The work was also supported by the University of Aberdeen Development Trust and by project grants from Friend of Anchor (RS2015 006), the British Heart Foundation (PG/15/82/31721), and a British Heart Foundation Fellowship (FS/11/2/28579) awarded to N.J.M.

The authors are indebted to Gizella Haramura (Faculty of Medicine, University of Debrecen, Debrecen, Hungary), Ágnes Bana (Faculty of Medicine, University of Debrecen, Debrecen, Hungary), and István Szász (Faculty of Medicine, University of Debrecen, Debrecen, Hungary) for the expert assistance. We also thank to Andrea Kovács-Paluska (Faculty of Medicine, University of Debrecen, Debrecen, Hungary) for her technical help.

Data Availability Statement

Not applicable


  • Humans
  • Foam Cells/metabolism
  • Plaque, Atherosclerotic/metabolism
  • Macrophages/metabolism
  • Atherosclerosis/metabolism
  • Lipoproteins, LDL/metabolism
  • Factor XIII/metabolism
  • Peptides/metabolism
  • foam cells
  • transglutaminase
  • enzyme-modified LDL
  • atherosclerotic plaque
  • macrophages
  • cross-linking
  • factor XIII
  • oxidized LDL
  • vascular smooth muscle cells


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